This project proposes to study the molecular structure, function and biosynthesis of proteoglycans in normal and abnormal connective tissues, primarily cartilage. Topics of present interest are: 1. The physical properties of monomer and aggregated proteoglycan preparations will be determined utilizing chromatographic, centrifugal and viscosimetric methods. Chemical and enzymatic modifications of proteoglycans will be used to study the chemical substructure of the macromolecules. 2. The characteristics of the interactions of proteoglycans with other matrix constituents will be studied. These interactions include the specificity of binding of proteoglycans to hyaluronic acid and small molecular weight proteins in the formation of proteoglycan aggregates and the interactions of proteoglycans with collagen during fibrillogenesis. 3. Radioisotopic precursors will be used to investigate the biosynthesis of the protein core and the polysaccharide portions of proteoglycan molecules. Model systems, such as the Swarm rat chondrosarcoma and chick limb bud chondrocyte cultures, will be studied to determine their usefulness for biosynthetic experiments.